Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer

Inclusion Criteria:

1. Aged after 18 years (18 is included).
2. Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hurthle cells, poorly differentiated carcinoma). At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors（RESCIST） version 1.1).
3. Disease progression within 12 months before inclusion.

4. Subjects must be 131I-refractory / resistant as defined by at least one of the following;

   • Lesions that do not demonstrate iodine uptake on any radioiodine scan;
   • Subjects received a single radioactive iodine therapy within 12 months (≥ 3.7 Giga Bequerel（GBq）[≥ 100 millicurie（mCi）]) and target lesion disease progression;
   • Every two radioactive iodine treatment interval <12 months, doses ≥ 3.7 GBq [≥100mCi], disease progress more than 12 months after at least once iodine therapy;
   • Received a total dose of radioactive iodine therapy ≥ 22.2 GBq (≥ 600 mCi);

5. Normal main organ function:

   • HB ≥ 90g / L;
   • ANC ≥1.5×109/L;
   • PLT ≥80×109/L;
   • BIL <1.5 × ULN;
   • ALT and AST <2.5 × ULN;
   • Cr≤1×ULN;
6. Eastern Cooperative Oncology Group（ECOG）Performance Status（PS） :0-2.
7. An expected survival of ≥ 3 months.
8. Pregnancy test (serum) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug.
9. Patient has to voluntarily join the study and sign the Informed Consent Form for the study.
10. Good compliance is expected, according to the program requirements follow-up and recorded adverse reactions.

Exclusion Criteria:

1. Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma).
2. Received VEGFR inhibitor (such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.) treatment within 1 months.
3. Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; coronary heart disease greater than Class II; II-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class II cardiac dysfunction.
4. Factors that could have an effect on oral medication (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction).
5. Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 3 months.
6. Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed.
7. Disposition evidence of thrombosis/bleeding in 2 month (despite severity), hemoptysis in 2 months (bright red blood, 1/2 teaspoon).
8. Arterial /venous thromboembolic events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism in the past 12 months.
9. Factors that could received radiotherapy or major surgery for anti - thyroid cancer in the past 28 days.
10. Factors that could received surgery (allows the full-recovery wound) or active hemorrhage, ulceration, intestinal perforation or intestinal obstruction in the past 28 days.
11. Uncontrolled infection.
12. Pregnant or lactating women.
13. Disposition evidence of depressive disorder (HAMD score ≥17).
14. Other conditions regimented at investigators' discretion.